ENHANCEMENT OF MITOMYCIN-C CYTO-TOXICITY TO HYPOXIC TUMOR-CELLS BY DICOUMAROL INVIVO AND INVITRO

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (1) , 213-216
Abstract
Dicoumarol can increase the enzymatic activation of mitomycin C (MC) to alkylating species by tumor cell sonicates under hypoxic conditions. To determine whether this increased generation of reactive metabolites would result in increased cytotoxicity, the effect of this combination on the viability of EMT6 cells treated in vitro under hypoxic and oxygenated conditions was studied. Dicoumarol increased the cytotoxicity of MC to these neoplastic cells under hypoxic conditions and decreased the toxicity of the antibiotic to aerobic cells. Dicoumarol might thus enhance the toxicity of MC to hypoxic cells of solid tumors, without increasing the toxic side effects of the antibiotic to the host. Treatment of EMT6 tumor-bearing animals with both dicoumarol and MC significantly decreased the survival of the radioresistant hypoxic tumor cells from that obtained with MC alone. In contrast, the leukopenia produced by the antibiotic was not exacerbated by the addition dicoumarol. A treatment regimen combining dicoumarol and MC might be a useful adjunct to radiation therapy for the eradication of the radioresistant hypoxic cells in solid tumors.